Differential roles of E-type cyclins during transformation of murine E2F-1-deficient cells

Hideshi Ishii, Koshi Mimori, Yasuji Yoshikawa, Masaki Mori, Yusuke Furukawa, Andrea Vecchione

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Deregulation of retinoblastoma gene product (pRB) is a hallmark of cancer, which acts as a transcriptional repressor by targeting E2F transcription factors. A transcription factor E2F-1 is not only important for S phase entry of cell cycle, but also stimulates gene expression of pro-apoptotic molecules. To investigate roles of E2F-1 and its target genes in cellular transformation, we studied murine E2F-1-deficient embryonic fibroblasts. Compared with control wild-type cells, E2F-1-deficient cells at early passages were less sensitive to exposure to γ-radiation and showed an increase of colony formation, while their growth was slow. After sequential passages, the growth of E2F-1-deficient cells reached closely to that of wild-type cells. Immunoblot study of E2F target genes showed that multiple passages of E2F-1-deficient cells resulted in preferential increase of cyclin E2 expression. Furthermore, carcinogenicity study using N-nitrosomethylbenzylamine demonstrated that, compared to wild-type mice, fore-stomach tumors in E2F-1-deficient mice expressed an increased amount of cyclin E2, but not cyclin E1. Taken together, the present study shows that differential roles of E-type cyclins are involved at least partially in the process of cellular transformation, supporting the concept of important roles of the E2F regulatory pathway in carcinogenesis.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalDNA and Cell Biology
Volume24
Issue number3
DOIs
Publication statusPublished - Mar 1 2005

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cell Biology

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